14 X-Ray Visible Embolic Beads (XEB) Microfluidic DeviceSize determined by nozzle size & flow ratePressurized system prevents clogging of nozzles at high generation ratesScale up by parallelization of device allows production of microbeads at rates of ~1 kHz.

15 XEB GenerationMicrobead production is performed at a slower rate to show the production of beads within the microfluidic device. An individual bead (arrow) is shown in successful frames every 5 ms moving down the channel.

16 SEM of XEBsNote uniformity of the microbeads based of scanning electron micrographs

17 Fundal Anatomy and Arterial MapHere is a diagram of the arterial supply to the fundusWe will target the three vessels that supply the fundusFor the purposes of our talk, we will call the Fundal, Left Gastric and Right Gastric-----Colon / SMA  enlarge to see vessel  fundus with shading L 0.9, T 1.4, R 1.6, B 1.0, H3.5H28 point or larger 1,2,3Pop – up boxes with 3 branchesWe will target its complete supply – the three locations noted here:

18 Beads: FabricationCustom made, barium sulfate containing, highly uniform alginate beads (~50 μm) served as the embolic agent in this study.Made with microfluidic devices with pressure controlled flow rates for uniform productionThe bead fabrication and properties were discussed in the previous lecture By Dr. KraitchmanThey are made on microfluidic devices with pressure controlled flow rates for uniform productionImportantly, they are fluoroscopically and CT visible, they are uniform, and they are small (50um)No Need for endogenous contrast during delivery

20 Celiac Axis GACE 1, Series 3Starting off, we perform a DSA on the celiac axisNote the angiogram corresponds to the diagramHere are the three target branchesFUNDALLEFT GASTRICRIGHT GASTRIC----Color three branches, red yellow greenGACE 1, Series 3

21 Approach to Site 1: Avoiding Reflux to SpleenWe are approaching the target site 1 – (what we are calling) the fundal arterySOS selective catheter, Renegade high Flow catheterIn this panel, there is contrast to target and also to spleenAdvancing, we position in site 1. We will have to control delivery rate to avoid backflow to spleen-----Now both 26 framesSeries 5: 6-36 (31 frames)Series 6: 7-29 (23 frames)

22 “Fundal Branch” EmbolizationPre-embolizationPost-embolizationPre and Post embolization at the fundal artery site 1Here is the SOS selective catheter, Renegade high Flow catheterIn this panel, you see the blushing of the target tissueAfter embolization, the blush is gone and the vessels are truncated-----Now series 6 and 16, each 26 framesSeries 6: 7-29 (23 frames)Series 15: 5-42 (38 frames)

23 Beads are Visible During DeliveryAs the beads have endogenous contrast, they can be visualized during deliveryHere is the tip of the renegade high flow catheterSite 1 – beads can be visulaized during deliveryThe are visualized with only their endogenous contrast---Note there is no contrast in injection – only opacity of beads is noted

24 Site 1: C-arm Cone Beam CT Pre Contrast PostSagittal Coronal AxialWith the C-arm cone beam CT we get more detailed information about the caseHere are: axial, coronal, sagital sectionsaxialThis is the stomach, the spleenCoronalsaggitalThis is the stomachOn this plan: Pre-embolization – we can visualize fundusOn this panel: we inject contrast to verify we are in the arterial supply to the fundal tissueOn this panel: we can see where the beads have been delvered  only to the fundus tissue, not the spleen or other organsWe verify targeting of fundus 3 dimensions in second panelIn the right panel, image of beads post-embolizationUse 2nd run for 25% contrast  update imagesChange DYNA  to CB CTGACE001_S19_DYNACT_POST_EMBO_1_AXIALGRAYSCALE1(want 3rd one that is embo site three in three planes)GACE 1, Series 7,19, 29

25 “Fundal Branch” CBCT Pre Contrast PostSagittal Coronal AxialWith the C-arm cone beam CT we get more detailed information about the caseHere are: axial, coronal, sagital sectionsaxialThis is the stomach, the spleenCoronalsaggitalThis is the stomachOn this plan: Pre-embolization – we can visualize fundusOn this panel: we inject contrast to verify we are in the arterial supply to the fundal tissueOn this panel: we can see where the beads have been delvered  only to the fundus tissue, not the spleen or other organsWe verify targeting of fundus 3 dimensions in second panelIn the right panel, image of beads post-embolizationUse 2nd run for 25% contrast  update imagesChange DYNA  to CB CTGACE001_S19_DYNACT_POST_EMBO_1_AXIALGRAYSCALE1(want 3rd one that is embo site three in three planes)GACE 1, Series 7,19, 29

26 “Fundal Branch” CBCT Post EmbolizationScrolling through the CBCT gives an idea of the extent of bead distribution from site 1This is a powerful intra-procedural confirmationNote the beads in site one, and no beads in other tissuesSite one, image of beads postembolization

27 Site 1: Bead are Visible During DeliveryAnother image of the beads being deliveredHere is the SOS Selective CatheterHere is the renegade high flow catheterHere are the beads being injectedYou can see the endogenous contrast of the beadsSite 1 – beads can be visulaized during deliveryThe are visualized with only their endogenous contrastSite one: Still image of beads during injection: (Stacked image)DSA with beads at 3 frames per secondGACE 1, Series 11

28 Left Gastric? GACE 1, Series 20, 21 Now we move to site twoWe choose the fundal vessel with fathom wire and advance renegade high flow catheterGACE 1, Series 20, 21

29 Site 2: C-Arm Cone Beam CTWe take a look with c-arm cone beam CT prior to embolization – this is a rotational angiogramWe want to verify the perfusion pattern of tissue downstream of the catheter8 s C-arm CBCT, 25% iohexal at 1cc/sec

30 Right Gastric EmbolizationPre EmbolizationPost EmbolizationWe moved on to site three – the Right GastricWe are approaching the target site 3 – (what we are calling) the right gastricSOS selective catheter, Renegade high Flow catheterIn this panel, you see the blushing of the target tissueAfter embolization, the blush is gone and the vessels are truncated------Advancing, we position in site 1. We will have to control delivery rate to avoid backflow to spleenMoving to Site three,Here are DSAsof the pre-and post DSAPre: 22post: 28

31 Embolization at Site 3 Post Embolization Pre EmbolizationStill images from site 3 – the right gastricHere is the Renegade high FlowIn this panel, you see the blushing of the target tissueAfter embolization, the blush is gone and the vessels are truncated------Moving to Site three,Here are still captures of the pre-and post DSADSA with 25% iohexal at 6 frames per second

32 Right Gastric CBCT Pre Contrast PostSagittal Coronal AxialWith the C-arm cone beam CT we get more detailed information about the caseHere are: axial, coronal, sagital sectionsAxialThis is the stomach, the spleen,beads delivered to site 1CoronalSaggitalThis is the stomach,On this plan: Pre-embolization – we can visualizefundus and ,On this panel: we inject contrast to verify we are in the arterial supply to the fundal tissueOn this panel: we can see where the beads have been delivered beads delivered to site 1,new beads delivered to site 3note that the beads have only been delivered to the fundus tissue, not the spleen or other organs,With C-arm cone beam CT,Top to bottom – axial, coronal, sagitalOn the left – pre embolization – you can see the beads from embolization at site 1In the center panel, we verify location in 3D with contrastIn this panel, we see the beads post-embo

33 Procedure Summary Pre Post “FB” Post RG Sagittal Coronal AxialReview of work at site 1 and site 3, C-arm cone beam CTHere are: axial, coronal, sagital sectionsaxialThis is the stomach, the spleenCoronalsaggitalThis is the stomachOn this panel: Pre-embolization – we can visualize fundusOn this panel: After treating site 1:we can visualize fundusbeads delivered to site 1,note there are no beads in other tissuesOn this panel: After treating site 1 and 3:beads delivered to site 3,On this panel: we can see where the beads have been delvered only to the fundus tissue, not the spleen or other organs,new beads delivered to site 3Trap in capillary bed contrast from previous DSAWill wash out as seen in site oneNot in this study  point of care / investigate further to see how the beads persist over time and their contrast persistCapitol P – pre and post  dyna ct to cbctLoop of 3 d scrollNow we move to site twoWe choose the fundal vessel with fathom wire and advance renegade high flowN= 3 swine

34 CBCT Post EmbolizationScrolling through the CT acquisition, we can see the extent of embolization in sites 1 and 3On this panel: After treating site 1 and 3:we can visualize fundusbeads delivered to site 1,beads delivered to site 3,note there are no beads in other tissuesThis is a powerful intra-procedural confirmation------Scrolling through the CBCT gives an idea of the extent of bead distribution from site 1

35 Return to Site #2 to Find Left GastricNow on our way out, we stop by site 2,Select the left gastric with the renegade high flowAnd confirmWent to site to access. Did not inject beads----Now we move to site twoWe choose the fundal vessel with fathom wire and advance renegade high flowWindowed for contrast (bead loss)Possible to access  but demonstrate possible

36 Gross PathologyAt the end of the procedure, we inject a histological stain - essential black dye – to mark the areas still perfusedWe sacrifice the animal and look at the gross pathologyThe pale areas have been embolized.see we hit the whole fundusThe dark areas still are perfusedThe entire fundus has been covered------the areas of preserved perfusion

37 Fundus 10x 2x Moving to histology….Here is an H&E of the gastric fundus at low power (2X)For orientation: mucosa, submucosa, muscularisThe arrows point to beads in arteries in the submucousaMoving to 10X, the beads are visible – a single bead in each vesselLow, Arrows, beads,Histological ImagesSee the 50 micron beads reach deep into the vascularute – lodging in the submucosaAnother image of the fundusBeads are hereAnother image, this time of the cardiaNo beads10x2x

38 Body2xHere is an H&E of the body of the stomach at low power (2X) – we did not target that areaFor orientation: mucosa, submucosa, muscularisThe arrows point to beads in arteries in the submucousaMoving to 10X, there are no beads evident in the vesselsLow, Arrows, beads,Histological ImagesSee the 50 micron beads reach deep into the vascularute – lodging in the submucosaAnother image of the fundusBeads are hereAnother image, this time of the cardiaNo beads10x

39 ConclusionsCombination of XEB and CBCT allows the interventional radiologist to:Better see where they are goingSee where they have beenAllows for complete fundal embolizationBetter assessment of treatment successes and failuresShould allow for “long term”Allow Interventional Radiologist to determine if re-embolization is neededIn conclusionFor bariatric embolization, to target the arterial supply to a specific part of the stomach, we used two methods to facilitate the workUniform, 50 micron (small), X-ray visible beadsso you can see the beads during delivery to modulate injection rate, reduce back flowso you know where you’ve been when making choosing subsequent targets and making future injectionsC-arm Cone Beam CTso you can visualize the soft tissuesvisualize the perfusion to the tissue of interestsee the beads afterwards in 3 dimension to be confident of the therapyTOGETHER THEY ALLOW FOR A SAFE AND COMPLETE EMBOLIZATION OF THE STOMACH-----allow visualization during and after delivery – so you know where you’ve beenTo know downstream targets, and get 3D confirmation of progress and remaining targts